Silk polymer-based adenosine release: Therapeutic potential for epilepsy

Andrew Wilz, Eleanor M. Pritchard, Tianfu Li, Jing Quan Lan, David L. Kaplan, Detlev Boison

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Adenosine augmentation therapies (AAT) make rational use of the brain's own adenosine-based seizure control system and hold promise for the therapy of refractory epilepsy. In an effort to develop an AAT compatible with future clinical application, we developed a novel silk protein-based release system for adenosine. Adenosine releasing brain implants with target release doses of 0, 40, 200, and 1000 ng adenosine per day were prepared by embedding adenosine containing microspheres into nanofilm-coated silk fibroin scaffolds. In vitro, the respective polymers released 0, 33.4, 170.5, and 819.0 ng adenosine per day over 14 days. The therapeutic potential of the implants was validated in a dose-response study in the rat model of kindling epileptogenesis. Four days prior to the onset of kindling, adenosine releasing polymers were implanted into the infrahippocampal cleft and progressive acquisition of kindled seizures was monitored over a total of 48 stimulations. We document a dose-dependent retardation of seizure acquisition. In recipients of polymers releasing 819 ng adenosine per day, kindling epileptogenesis was delayed by one week corresponding to 18 kindling stimulations. Histological analysis of brain samples confirmed the correct location of implants and electrodes. We conclude that silk-based delivery of around 1000 ng adenosine per day is a safe and efficient strategy to suppress seizures.

Original languageEnglish (US)
Pages (from-to)3609-3616
Number of pages8
JournalBiomaterials
Volume29
Issue number26
DOIs
StatePublished - Sep 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

Keywords

  • Adenosine
  • Brain
  • Controlled drug release
  • Drug delivery
  • Epilepsy
  • Silk

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